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Biomedical subjects

A Anelli

Publications and source records attributed to A Anelli.

At least 19 recordsLinked to original sources
PubMed2003

Correlation of p53 status with outcome of neoadjuvant chemotherapy using paclitaxel and doxorubicin in stage IIIB breast cancer.

BACKGROUND: The role of p53 in modulating apoptosis has suggested that it may affect efficacy of anticancer agents. We prospectively evaluated p53 alterations in 73 patients with locally advanced breast cancer (IIIB) submitted to neoadjuvant chemotherapy. PATIENTS AND METHODS: Patients received three cycles of paclitaxel (175 mg/m2) and doxorubicin (60 mg/m2) every 21 days. Tumor sections were analyzed before treatment for altered patterns of p53 expression using immunohistochemistry and DNA sequencing. RESULTS: An overall response rate of 83.5% was obtained, including 15.1% complete pathological responses. The regimen was well tolerated with 17.7% grade 2/3 nausea and 12.8% grade 3/4 leukopenia. There was a statistically significant correlation between response and expression of p53. Of the 25 patients who obtained a complete clinical response, two were classified as positive (P = 0.004, chi-square). Of 11 patients who obtained a complete pathological remission, one was positive (P = 0.099, chi-square). Discussion The combination is highly effective in locally advanced breast cancer. A negative expression of p53 indicates a higher chance of responding to this regimen. The p53 status may be used as a biological marker to identify those patients who would benefit from more aggressive treatments.

Adult↗
PubMed2001

A phase II trial of fractionated vinorelbine/doxorubicin as first-line therapy for advanced breast cancer.

In western countries breast cancer is still the leading cause of death of women. Very promising results have been obtained by combining vinorelbine and doxorubicin, two of the most active drugs in metastatic breast cancer. However, despite the activity reported, this combination has shown a 10% rate of grade 2-4 cardiac toxicity, mainly due to the total cumulative doses of anthracycline delivered. The aim of this study was to divide the total dose of doxorubicin into two administrations on days 1 and 8, in order to cut down its toxicity while maintaining the same activity. Fifty-two chemotherapy naïve patients with metastatic breast cancer entered into the study and were treated with vinorelbine 25 mg/m2 plus doxorubicin 25 mg/m2 both on days 1 and 8 every three weeks. Fifty-one patients were eligible and evaluable for toxicity while 47 of them were evaluable for activity. Haematological toxicity was predominantly related to neutropenia, with grade 3/4 in 16% of cycles. Non-haematological toxicity was represented by alopecia grade 3 (which affected 65% of the patients), local phlebitis and severe constipation. No clinically significant cases of neuropathy or cardiac dysfunction were seen. With regard to activity, 38 out of 47 patients (80%) responded to therapy, nine of them achieving complete responses (19%). Median response duration was 16 months and the median overall survival was 22.7 months. We conclude that the fractionated administration of vinorelbine and doxorubicin is associated with excellent haematological and non-haematological tolerability (especially as regards cardiac toxicity), coupled with high levels of activity comparable to those observed using regimens based on unfractionated administration of treatment.

Alopecia↗
PubMed1995

Mutations of the p53 gene in male breast cancer.

BACKGROUND: Cancer of the male breast (MBC) is rare, accounting for less than 1% of cancer in males and representing less than 1% of all breast cancers. Reports of abnormalities in the expression of the tumor suppressor gene p53 in MBC have been few. METHODS: To assess the expression and mutations of the p53 gene, 35 patients with 36 MBC (one patient with bilateral breast carcinoma) were examined using immunohistochemical methods, polymerase chain reaction (PCR)-single strand conformation polymorphism and DNA sequencing. RESULTS: Thirty-one of the 36 carcinomas were studied by immunohistochemistry and by the PCR-based approach. Five patients were studied by immunohistochemistry only. Twelve patients (41.4%) of the 29 studied by molecular analysis presented an altered pattern in the single strand conformation polymorphism gel and point mutations were confirmed in all by direct DNA sequencing. Thirty-six tumors were studied by immunohistochemistry and 2 (5.5%) patients showed overexpression of the p53 protein. There were no statistically significant differences in p53 status with respect to: age, stage, estrogen receptors, progesterone receptors, tumor type. Patients with normal p53 showed a predisposition, although not statistically significant, for a longer disease free survival (5.6 years versus 4.2 years) and overall survival (5.9 years versus 4.8 years) than did patients with genetically altered p53. CONCLUSIONS: The incidence of male patients detected with p53 mutations (41.4%) in this series is concordant with the incidence of p53 mutations in female breast cancer, supporting the idea that cancer of the male breast is similar to the female counterpart.

Age Factors↗
PubMed1995

Analysis of MTS1/CDK4 in female breast carcinomas.

Multiple factors, both environmental and genetic, are thought to play roles in breast carcinogenesis. The recently cloned multiple tumor suppressor gene (MTS1), the product of which interacts with CDK4 to regulate cell growth, has been found to be mutated with high frequency in a variety of cell lines as well as primary tumors of different histologic types. Using PCR-SSCP, we analyzed exons one (126 bp) and two (307 bp) of the MTS1 gene to determine the incidence of mutation in a population of 50 primary breast adenocarcinomas and corresponding normal tissue. Analysis of five breast tumor cell lines was also performed. We found no mutations in the MTS1 gene in the primary breast tumor samples. One cell line was found to have a homozygous deletion of the gene. Our results suggest that the MTS1 gene is not mutated with increased frequency in primary breast tumors, and thus may not play a major role in breast carcinogenesis.

Adenocarcinoma↗
PubMed1995

A prospective randomized evaluation of three schedules of mesna administration in patients receiving an ifosfamide-containing chemotherapy regimen: sustained efficiency and simplified administration.

Chemotherapy with oxazaphosphorines, such as ifosfamide, is often limited by unacceptable urotoxicity. Without uroprotection hemorrhagic cystitis becomes dose-limiting. Mesna, a thiol compound, is a drug able to bind the toxic metabolites, forming nontoxic compounds in the urine. A total of 122 patients were enrolled in this study and 228 chemotherapy cycles with an ifosfamide-containing regimen were performed (225 evaluable). Mesna was given at the same total dose as the ifosfamide in all arms. On arm A, mesna was given i. v. in equal doses 15 min before and 4 h and 8 h following the ifosfamide dose. On arm B, mesna was given in three equivalent doses 15 min before (i.v.) and 4 h (i.v.) and 8 h (p.o., double dose) following ifosfamide. On arm C, mesna was given i.v. in two equal doses given 15 min before and 4 h following. The incidence of urotoxicity was very low (lower than 15%) in the three arms, 0% in A, 1.36% in B and 2.70% in C. All three arms were equally efficient. Schedule C was considered superior to the others, since it was equally effective, simpler and more convenient.

Adolescent↗
PubMed1995

Microdissection and molecular genetic analysis of HER2/neu in breast carcinoma.

Precise correlation of histomorphology with molecular genetic analysis is difficult in tissues composed of heterogeneous cell populations. We describe here a novel microdissection technique employed to correlate HER2/neu (HER2) immunohistochemical staining with HER2 genetic analysis in formalin-fixed, paraffin-embedded breast tissue. Fourteen invasive ductal carcinomas were selected from the pathology files of Memorial Sloan-Kettering Cancer Center that had been immunostained for HER2. Seven tumors showed typical membrane immunoreactivity and seven were negative. A dissecting microscope was then used to isolate minute (< or = 1 mm x 1 mm) areas of invasive carcinoma and normal breast tissue for molecular study. To document the type of cell sample submitted for polymerase chain reaction (PCR) analysis, each microdissected piece of tissue was photographed prior to removal from the glass slide. A preliminary study of four cases compared the results of PCR and genetic analysis using microdissected hematoxylin and eosin (H & E)-stained tissue, unstained dewaxed tissue, and destained dewaxed tissue in four specimens. Similar results were obtained with all three tissue preparations. Thereafter, H & E stained sections were selected as the tissue preparation of choice because tissue details were seen more clearly. There was complete correlation of immunohistochemical staining and HER2 analysis by PCR in all 14 cases. In the final 10 cases, the PCR product was resolved by gel electrophoresis and quantified by optical densitometry. Fourfold to eightfold amplification of HER2 was found in the five tumor specimens that immunohistochemically stained for HER2. A single copy of HER2 was found in all HER2-negative tumors and in normal breast tissue. We conclude that it is possible to quantify gene amplification of HER2 in minute samples of H & E-stained normal and malignant breast tissue. This microdissection technique can be applied to correlative histologic--molecular genetic analysis in a wide variety of tumor types.

Breast Neoplasms↗
PubMed1994

Tamoxifen administration is associated with a high rate of treatment-limiting symptoms in male breast cancer patients.

BACKGROUND: Although an uncommon disease, male breast cancer (MBC) will be responsible for 300 deaths in 1993 in the United States. Because of the high rate of estrogen receptor positivity in males, adjuvant hormonal therapy with tamoxifen in the adjuvant setting has been used widely. Little is known about the side effects of this estrogen receptor blocker in males. METHODS: The authors evaluated the side effects of adjuvant tamoxifen treatment in 24 patients (19 of whom were estrogen receptor positive) treated at the authors' institution between 1990 and 1993. RESULTS: Fifteen (62.5%) patients reported at least one side effect. The most common side effect was a decrease in libido, which occurred in 7 (29.2%) patients; followed by weight gain, which occurred in 6 (25%) patients; hot flashes, which occurred in 5 (20.8%); mood alterations, which occurred in 5 (20.8%); depression, which occurred in 4 (16.6%); insomnia, which occurred in 3 (12.5%); and deep venous thrombosis, which occurred in 1 (4.2%). Five (20.8%) patients terminated treatment with tamoxifen in less than 1 year because of these side effects. Two of these patients had decreased libido, two had hot flashes, and one suffered deep venous thrombosis. CONCLUSIONS: In contrast to female breast cancer patients, who have a 4% attrition rate to adjuvant tamoxifen treatment, MBC patients have a 20.8% attrition rate related to side effects of tamoxifen treatment.

Adult↗
PubMed1994

Complement activation in dialysis: effects on cytokines, lymphocyte activation and beta 2 microglobulin.

Anaphylatoxins generated by complement activation by filter membranes are present in plasma during hemodialysis (HD). In the presence of endotoxins which may contaminate the dialysate, they can trigger monocytes to produce interleukin-1 (IL-1) and tumor necrosis factor (TNF), with detrimental effects for the patients. We have investigated whether or not the use of complement activating (cuprophan) and non- (or less-) activating membranes (polysulfone, polymethylmethacrylate or polyacrylonitrile) per se influences cytokine levels in HD patients. Our results indicate that if a sterile bicarbonate solution is used as dialysate, there are no significant increases in IL-1, TNF, interleukin-2 (IL-2) and soluble IL-2 receptors (sIL-2r) throughout HD, even with cuprophan membranes. Moreover even a prolonged use of this membrane (three months) did not change pre-dialysis levels of cytokines and receptors. Use of complement activating membranes also does not influence beta 2 microglobulin levels.

Acrylic Resins↗
PubMed1991

Purification and partial characterization of a new 85 KDa amyloidosis-related protein in chronic hemodialysis.

An 85 KDa protein was purified by a multistep procedure (ultracentrifugation, HPLC, SDS-PAGE) from sera and amyloid deposits of patients on chronic hemodialysis and was characterized as a novel protein on the basis of its NH2 terminus (KVQLVE-V). This protein was formed by two subunits with Mr of 55 and 30 KDa and had affinity for Thyoflavin T, a fluorescent dye which was employed for labelling the protein prior HPLC. The 85 KDa was the only fluorescent component of ultracentrifugates from the serum of hemodialyzed patients while in amyloid fibrils it coexisted in roughly equimolar amounts with beta 2-microglobulin. This new high molecular weight protein which accumulates in uremia, could be co-responsible with beta 2-microglobulin for hemodialysis-related osteoarticular amyloidosis.

Amino Acid Sequence↗
PubMed1991

Desferrioxamine infusion can modify EEG tracing in haemodialysed patients.

Neurological derangement has been reported in haemodialysed patients receiving intravenous desferrioxamine (DFO) for aluminium-related disorders. The possible direct effects of desferrioxamine on EEG recordings were investigated in ten haemodialysed patients who underwent a DFO test 2 h after the end of dialysis. According to a commonly accepted protocol, 40 mg/kg body-weight of desferrioxamine was infused in 60 min. EEG recording was continuously performed, starting 30 min before and stopping 30 min after the desferrioxamine infusion. Besides visual inspection, EEG records were digitised, tapered, and spectrally analysed with Digital PDP 11/73 microcomputer. Basal EEG recording was normal in all patients. In three patients a progressive EEG slowing was detected by visual inspection during desferrioxamine infusion; in these cases automatic analysis revealed a 50% increase in power of slower frequencies 30 min after starting the infusion, when no changes in plasma aluminium concentrations are detected; a complete recovery was observed 30 min after desferrioxamine withdrawal. In one patient bilateral paroxysms of slow waves appeared, so we stopped desferrioxamine infusion. Two of the three patients who developed EEG abnormalities also had an increased aluminium body burden (positive DFO test). Results indicated that desferrioxamine per se can modify EEG in haemodialysis patients and that its effect is not mediated by acute increases of plasma aluminium concentrations. The finding of a positive DFO test in two of three patients with EEG changes may suggest that an aluminium-induced blood-brain barrier derangement could have played a role. However, prompt recovery after ceasing desferrioxamine infusion strongly suggests a direct role of desferrioxamine in the induction of EEG changes.(ABSTRACT TRUNCATED AT 250 WORDS)

Aluminum↗
PubMed1991

[Use of echography for the diagnosis of joint amyloidosis in dialyzed patients].

Amyloid arthropathy is an important complication of long-term hemodialysis. This condition may lead to destructive bone lesions and to severe functional impairment. We studied with sonography of both knees 32 long-term dialysis patients (mean dialytic age: 69.7 months), whose 7 were carrying palpable joint swellings. In 29/32 patients, ultrasound scans were associated with knee X-rays films, patellar views included. In one case, opaque arthrography was performed too. Sonography demonstrated the presence of fluid collections within the articular space and the synovial cavities in 19/32 patients (59%). Their content was transonic or mildly hypoechoic. X-ray films were positive for amyloid bone involvement in 19/29 cases (66%), with intra-osseous cysts and cortical erosions. There was a good general agreement between the results obtained with the two techniques: therefore, in some cases only one examination was positive. Sonography is proposed, in association with standard X-ray films, as a simple and reliable method for the diagnosis of articular amyloidosis in dialysis patients and for the follow-up of this disease.

Amyloidosis↗
PubMed1989

Substitution of calcium carbonate for aluminum hydroxide in patients on hemodialysis. Effects on acidosis, on parathyroid function, and on calcemia.

Substitution of calcium carbonate for aluminum hydroxide in patients on dialysis: effects on acidosis, parathyroid function, and calcemia. We studied the effects of substituting CaCO3 for aluminum-containing gels on metabolic acidosis and on the response of the parathyroid glands in 11 patients treated with chronic hemodialysis. The 8 men and 3 women were clinically stable, were known to be compliant, and had no clinical evidence of aluminum overload; they were not receiving vitamin D supplements; and they had been on dialysis for an average of 65.6 months (range: 13-188 months). After 3 weeks of CaCO3 administration plasma phosphate concentration remained well controlled, and plasma calcium concentration increased from 9.2 +/- 0.2 (2.3 +/- 0.1 mmol/l) to 10.1 +/- 0.2 mg/dl (2.5 +/- 0.1 mmol/l). Predialysis plasma bicarbonate concentration increased from 19.7 +/- 0.6 to 21.9 +/- 0.6 mmol/l. Plasma aluminum concentration decreased from 78.7 +/- 12.5 to 48.5 +/- 3.9 micrograms/l. Plasma PTH level increased from 2.0 +/- 0.7 to 3.3 +/- 0.8 ng/ml despite the concurrent increase in plasma calcium levels. All values returned to control levels following discontinuation of CaCO3 and resumption of aluminum gels. We conclude: (1) In addition to controlling hyperphosphatemia and increasing plasma calcium concentration, CaCO3 ameliorates metabolic acidosis. (2) Avoidance of oral aluminum intake is followed by prompt lowering of plasma aluminum levels. (3) PTH levels paradoxically increase despite the increment in plasma calcium concentration. The hypercalcemia seen with CaCO3 administration may be due, in part, to transient parathyroid hypersecretion that develops when aluminum administration is discontinued.

Acidosis↗